COVID-19 Rapid Guideline in Kidney Transplant Recipients.
in the reports presented about COVID-19, patients receiving kidney transplantation have not been specifically studied and based on national flowchart, this population is classified as highrisk group, thus it is necessary to be aware of the step-by-step treatment approach of these patients. Suspicious cases included patients with a history of dry cough, chills or sore throat accompanying by shortness of breath with or without fever, patients with upper/lower respiratory symptoms with radiological manifestations as single or double-sided multilobular infiltrations on CT scan or plain chest radiography, any one that has a history of close contact with a definite COVID-19 case within the last 14 days, any one with a history of presence in COVID-19 epidemic regions within the last 14 days and patient with pneumonia that despite of proper treatment has an inappropriate clinical response and clinical condition becomes more severe in an unusual way or unexpectedly.


Recombinant sickle hemoglobin containing a lysine substitution at Asp-85(alpha): expression in yeast, functional properties, and participation in gel formation.
Clinical modalities based on inhibition of gelation of HbS are hindered by the lack of quantitative information on the extent of participation of different amino acid residues in the aggregation process. One such site is Asp-85(alpha), which is involved in a parallel interdouble strand ionic interaction with Lys-144(beta) according to the crystal structure of HbS, but electron microscopy does not specifically show Asp-85(alpha) as a contact site for fiber formation. Using a yeast recombinant system, we have substituted this site by Lys to abolish ion pairing and to make a quantitative determination of its participation in aggregation. The purified double mutant was shown to have the expected pI, the calculated molecular weight, correct amino acid composition, and peptide map. The recombinant double mutant has an oxygen affinity of 10 mm Hg, which is identical to that for HbA and HbS under the same conditions; it also has high cooperativity with an average n value of 2.7. The change in P50 in response to chloride ions was about 25% less than that for HbA or HbS and is ascribed to the introduction of a new positive charge near one of the major oxygen-linked chloride binding sites of hemoglobin. The gelation concentration of the double mutant was measured by a new procedure (Bookchin et al, 1994); the maximal amount of soluble hemoglobin (Csat) in the presence of dextran indicated a decreased tendency for gelation with a Csat of 53 mg/mL compared with 34 mg/mL for HbS. This inhibitory effect is smaller than that of the E6V(beta)/L88A(beta) (Csat, 67 mg/mL) and the E6V(beta)/K95I(beta) (Csat, 90 mg/mL) recombinant hemoglobins. Thus, we would classify Asp-85(alpha) as a moderate contributor to the strength of the HbS aggregate. This wide range of gelation values demonstrates that some sites are more important than others in promoting HbS aggregation.


A Core-Shell Nanoplatform for Synergistic Enhanced Sonodynamic Therapy of Hypoxic Tumor via Cascaded Strategy.
Sonodynamic therapy (SDT) always causes tumor hypoxia aggravation which can induce malignant cell proliferation and drug resistance. To overcome these disadvantages, a cascaded drug delivery system (Lipo/HMME/ACF@MnO2 -AS1411) is constructed for synergistic enhanced sonodynamic therapy. First, hematoporphyrin monomethyl ether (HMME) and acriflavine (ACF) are encapsulated in the lipid layers and the inner aqueous cores of the liposomes, respectively. Then the ultrathin manganese dioxide (MnO2 ) nanosheets are coated on the surface of the liposomes by using KMnO4 and polyethylene glycol through "one step reduction and modification" method. Furthermore, the nanoparticles are decorated with tumor-targeting AS1411 aptamer through the phosphate groups on the DNA strand which can bind to Mn sites to obtain Lipo/HMME/ACF@MnO2 -AS1411 delivery system. Herein, HMME can act as a sonosensitizer, and ACF is used to prevent the formation of HIF-1α/HIF-1β dimerization to overcome the negative effects after SDT. The Lipo/HMME/ACF@MnO2 -AS1411 delivery system has multiple functions, including codelivery of HMME and ACF, pH/glutathione/ultrasound triple responses, synergistic cascaded enhancement of SDT, precise tumor-targeting, and magnetic resonance imaging. The in vitro and in vivo results suggest that the Lipo/HMME/ACF@MnO2 -AS1411 delivery system is a promising core-shell nanoplatform for synergistic enhancement of sonodynamic therapy, which can provide a new approach in the related research fields.


Having versus doing: The roles of moral identity internalization and symbolization for prosocial behaviors.
Moral identity has been identified as a consistent predictor of prosocial behavior, but the specific relationship and predictive strength of its two dimensions, internalization ("having") and symbolization ("doing"), are less clear. The current article explores this through two self-report studies. In study 1 (N = 228) a series of hierarchical regression analyses showed that, for three out of four domains of prosocial behavior, symbolization was the only significant predictor, and that its strength differed across outcomes. Building on these results, Study 2 (N = 299) proposed that the observed vs. anonymous nature of prosocial behavior could account for these differences. Unexpectedly, symbolization predicted both public and private behaviors, whereas internalization generally did not. Significant interactions between internalization and symbolization were also observed. These findings are discussed in relation to their theoretical implications and future moral identity research.


Stability and binding properties of a modified thrombin binding aptamer.
Aptamer-based drugs represent an attractive approach in pharmacological therapy. The most studied aptamer, thrombin binding aptamer (TBA), folds into a well-defined quadruplex structure and binds to its target with good specificity and affinity. Modified aptamers with improved biophysical properties could constitute a new class of therapeutic aptamers. In this study we show that the modified thrombin binding aptamer (mTBA), (3')GGT(5')-(5')TGGTGTGGTTGG(3'), which also folds into a quadruplex structure, is more stable than its unmodified counterpart and shows a higher thrombin affinity. The stability of the modified aptamer was investigated using differential scanning calorimetry, and the energetics of mTBA and TBA binding to thrombin was characterized by means of isothermal titration calorimetry (ITC). ITC data revealed that TBA/thrombin and mTBA/thrombin binding stoichiometry is 1:2 for both interactions. Structural models of the two complexes of thrombin with TBA and with mTBA were also obtained and subjected to molecular dynamics simulations in explicit water. Analysis of the models led to an improvement of the understanding of the aptamer-thrombin recognition at a molecular level.


Peri-implantitis at implants with different diameters: a pilot study in dogs.
To evaluate the progression of an induced peri-implantitis at implants with different diameters and the outcome of a corrective surgical debridement. Three months after the extraction of the mandibular premolars and first molars in six dogs, non-submerged narrow implants (3.3 mm in diameter) or standard implants (3.8 mm and 4.1 mm) were installed in the molar regions, bilaterally. After 3 months, peri-implantitis lesions were induced with ligatures and plaque accumulation for 3 months. Plaque accumulation was allowed for a further month after ligatures removal. A surgical mechanical decontamination of the surfaces was subsequently performed using gauzes soaked in saline and irrigation. Five months after, biopsies were retrieved and histological slides prepared. X-rays were taken at treatment and 5 months after. Fourth months after peri-implantitis induction, 2.2 ± 1.0 mm at the standard implants and 3.2 ± 0.4 mm at the narrow implants were observed. Five months after treatment, a mean gain of marginal bone of 0.5 ± 0.6 mm was obtained at the standard implants and of 0.9 ± 0.4 at the narrow implants (p = 0.249). The vertical and horizontal defects were found partially closed. At the histological analysis, the coronal level of osseointegration after 5 months of healing was at 2.1 ± 0.8 mm at the standard implants, and 2.8 ± 0.3 mm at narrow implants (p = 0.116). In conclusion, the narrow implants showed a tendency of a faster progression of the induced peri-implantitis compared to standard implants. The implant diameter did not influence the outcome of a surgical treatment of an induced peri-implantitis.


Machine perfusion in liver transplantation: an essential treatment or just an expensive toy?
This review focuses on recent developments in preservation techniques in liver transplantation. First, we discuss mechanisms of organ injury when using high-risk organs, including donation after circulatory death and steatotic grafts and we summarize pathways of ischemia reperfusion injury together with their link to the immune response. Second, we report on improvement strategies of marginal liver grafts by different machine perfusion concepts and summarize perfusion approaches with recent clinical implementation.


Magnonic Casimir Effect in Ferrimagnets.
Quantum fluctuations are the key concepts of quantum mechanics. Quantum fluctuations of quantum fields induce a zero-point energy shift under spatial boundary conditions. This quantum phenomenon, called the Casimir effect, has been attracting much attention beyond the hierarchy of energy scales, ranging from elementary particle physics to condensed matter physics together with photonics. However, the application of the Casimir effect to spintronics has not yet been investigated enough, particularly to ferrimagnetic thin films, although yttrium iron garnet (YIG) is one of the best platforms for spintronics. Here we fill this gap. Using the lattice field theory, we investigate the Casimir effect induced by quantum fields for magnons in insulating magnets and find that the magnonic Casimir effect can arise not only in antiferromagnets but also in ferrimagnets including YIG thin films. Our result suggests that YIG, the key ingredient of magnon-based spintronics, can serve also as a promising platform for manipulating and utilizing Casimir effects, called Casimir engineering. Microfabrication technology can control the thickness of thin films and realize the manipulation of the magnonic Casimir effect. Thus, we pave the way for magnonic Casimir engineering.


Placement of a collagen glaucoma drainage device to control intraocular pressure and chronic iritis secondary to juvenile rheumatoid arthritis.
A patient with juvenile rheumatoid arthritis and chronic iritis is reported with intraocular pressure near 30 mm Hg and previous episodes of intraocular pressure as high as 50 mm Hg despite maximally tolerated medical therapy. Because of the potential risk involved with a full-thickness filtration procedure, it was decided that a nonpenetrating deep sclerectomy would be appropriate, followed by placement of a collagen glaucoma drainage device to maintain aqueous outflow. Immediately postoperatively, intraocular pressure was stabilized. At 24 months postoperatively, intraocular pressure was well controlled at 15 mm Hg with patient receiving only Lotemax. No significant complications were noted at any point in the postoperative course. Because of the patient's predisposition for serious complications frequently associated with trabeculectomy, nonpenetrating deep sclerectomy with the collagen glaucoma drainage device was an effective alternative for this patient.


Pathophysiology of portal hypertension and esophageal varices.
Esophageal varices are the major complication of portal hypertension. It is detected in about 50% of cirrhosis patients, and approximately 5-15% of cirrhosis patients show newly formed varices or worsening of varices each year. The major therapeutic strategy of esophageal varices consists of primary prevention, treatment for bleeding varices, and secondary prevention, which are provided by pharmacological, endoscopic, interventional and surgical treatments. Optimal management of esophageal varices requires a clear understanding of the pathophysiology and natural history. In this paper, we outline the current knowledge and future prospect in the pathophysiology of esophageal varices and portal hypertension.


Radiation occupational health interventions offered to radiation workers in response to the complex catastrophic disaster at the Fukushima Daiichi Nuclear Power Plant.
The Fukushima Daiichi Nuclear Power Plant (NPP) 1 was severely damaged from the chain reaction of the Great East Japan Earthquake and Tsunami on 11 March 2011, and the consequent meltdown and hydrogen gas explosions. This resulted in the worst nuclear accident since the Chernobyl accident of 1986. Just as in the case of Chernobyl, emergency workers were recruited to conduct a wide range of tasks, including disaster response, rescuing activities, NPP containment, and radiation decontamination. This paper describes the types and efficacy of the various occupational health interventions introduced to the Fukushima NPP radiation workers. Such interventions were implemented in order to prevent unnecessary radiation overexposure and associated adverse health effects and work injuries. Less than 1% of all emergency workers were exposed to external radiation of >100 mSv, and to date no deaths or health adversities from radiation have been reported for those workers. Several occupational health interventions were conducted, including setting of new regulatory exposure limits, improving workers' radiation dosimetry, administration of stable iodine, running an occupational health tracking system, and improving occupational medicine and preventative care. Those interventions were not only vital for preventing unnecessary radiation, but also for managing other general health issues such as mental health, heat illness and infectious diseases. Long-term administration of the aforementioned occupational health interventions is essential to ensure the ongoing support and care for these workers, who were put under one of the most severe occupational health risk conditions ever encountered.


Induction of Cellular Differentiation and Single Cell Imaging of Vibrio parahaemolyticus Swimmer and Swarmer Cells.
The ability to study the intracellular localization of proteins is essential for the understanding of many cellular processes. In turn, this requires the ability to obtain single cells for fluorescence microscopy, which can be particularly challenging when imaging cells that exist within bacterial communities. For example, the human pathogen Vibrio parahaemolyticus exists as short rod-shaped swimmer cells in liquid conditions that upon surface contact differentiate into a subpopulation of highly elongated swarmer cells specialized for growth on solid surfaces. This paper presents a method to perform single cell fluorescence microscopy analysis of V. parahaemolyticus in its two differential states. This protocol very reproducibly induces differentiation of V. parahaemolyticus into a swarmer cell life-cycle and facilitates their proliferation over solid surfaces. The method produces flares of differentiated swarmer cells extending from the edge of the swarm-colony. Notably, at the very tip of the swarm-flares, swarmer cells exist in a single layer of cells, which allows for their easy transfer to a microscope slide and subsequent fluorescence microscopy imaging of single cells. Additionally, the workflow of image analysis for demographic representation of bacterial societies is presented. As a proof of principle, the analysis of the intracellular localization of chemotaxis signaling arrays in swimmer and swarmer cells of V. parahaemolyticus is described.


Patient-Specific Implants in Oculofacial Plastic Surgery.
To investigate how patient-specific implants (PSIs) are being utilized for periocular facial skeletal reconstruction. Specifically, to characterize indications for custom implants, areas of reconstruction, intraoperative variables impacting implant placement, as well as to report on postoperative outcomes. A retrospective chart review was performed for patients who received a PSI for periocular skeletal reconstruction between 2015 and 2019. Three independent academic centers were included in this study, which encompassed 4 different primary surgeons. Medical records, radiographic imaging, and operative reports were reviewed. Eleven patients, 8 females and 3 males, ages ranging from 15 to 63 years old received PSIs. The average duration of follow up was 16 months ± 6.6 months (range: 9-30 months). The most common underlying etiology for reconstruction was prior trauma (54.5%) followed by benign tumor resection (18.2%). The most frequent area of reconstruction involved the inferior orbital rim and adjacent maxilla (63.6%). Implant materials included porous polyethylene, polyetheretherketone, and titanium. Six implants required intraoperative modification, most commonly accommodate critical neurovascular structures (66.6%) or improve contour (33.3%). Two postoperative complications were noted, both in the form of infection with 1 implant requiring removal. Reconstruction of complex facial skeletal defects can be achieved by utilizing computer-assisted design software and 3D printing techniques to create PSIs. These implants represent the most customizable option for symmetric restoration of the facial skeleton by not only addressing structural deficits but also volumetric loss. This was particularly apparent in reconstruction of the orbital rim and midface. PSIs were found to be of most benefit in patients with prior trauma or complex skeletal defects after tumor resection.


Statistical analysis of case-control studies.
Methods of analysis of results from case-control studies have evolved considerably since the 1950s. These methods have helped to improve the validity of the conclusions drawn from case-control research and have helped to ensure that the available data are utilized to their fullest extent. Logistic regression modeling, in its various forms, has become by far the most frequently applied method for multivariable analysis of case-control studies. As with any type of statistical modeling, the appropriateness of its formulation can be verified only partially through examination of the data themselves, and cautious interpretation has been urged (80-83). In this article, I have concentrated on methods that are extremely well suited to the evaluation of fairly specific etiologic issues, where one or two particular exposures are designated as being of a priori interest. In situations where a large number of associations are examined for possible case-control differences, additional complexities arise. Several authors have argued strongly against statistical adjustment for "multiple comparisons" in such situations (6, 7, 84). However, recent work suggests that, when background information is limited, certain forms of multiple-comparison procedures can be useful, specifically within a decision-analysis framework (85-87). Further methodological work relevant to the analysis of case-control studies is needed in at least two important areas. First, as discussed above, we need additional methods for conducting analyses that take appropriate account of the considerable error to which measurements in case-control studies are subject. Only with such methods available can estimates from case-control studies be confidently employed for elucidating pathogenesis, for developing policy, and for individual decision-making. Second, there has been a renewed effort in recent years to clarify the nature of causal effects and to relate these to the typically calculated epidemiologic parameters (88-92). As this work develops further, it is likely that the analysis of case-control studies will be enriched.


Clinical profile & complications of neurotoxic snake bite & comparison of two regimens of polyvalent anti-snake venom in its treatment.
The optimal anti-snake venom (ASV) dose required to treat neurotoxic snake envenomation is not known. Low-dose ASV (national protocol: maximum dose 200 ml) may be as efficacious as the conventional regimen (100 ml six hourly till all symptoms disappear), but a direct comparison of the regimens is not available. The aim of this study was to test the efficacy of low-dose ASV regimen against the conventional high-dose regimen. The clinical profile of 51 patients with neurotoxic snake envenomation was studied. Patients were treated with either the national protocol or the conventional protocol for ASV administration. The time to complete recovery of symptoms, duration of mechanical ventilation and total dose of ASV were compared. More patients were females (28 vs. 23) bitten in the early morning hours (2400-0600 h). Thirty nine of 51 (76.4%) patients required mechanical ventilation. In terms of progression of neuroparalysis, time to complete resolution of ptosis and occurrence of VAP and ASV reactions, there was no difference. Duration of mechanical ventilation was less with the national protocol (24 vs. 43.5 h). Significantly less amount of ASV was used with the national protocol (224 vs. 982 ml) per patient. There were no mortality or permanent neurological sequelae with either regimen. In this preliminary study, it was found that the national ASV protocol was as effective as the conventional regimen for neurotoxic snake bites. However, the findings need to be tested in a larger randomized controlled trial for definitive conclusions.


Effects of Panax ginseng on the nerve growth factor expression in testosterone induced benign prostatic hyperplasia.
The prostatic hyperplasia in benign prostatic hyperplasia (BPH) leads to obstructive micturition symptoms. Previous studies showed that pontine micturition center (PMC), ventrolateral periaqueductal gray (vlPAG), and medial preopticnucleus (MPA) regions in the brain have been known to regulate the urinary bladder function. The present study shows the influences of Panax ginseng on nerve growth factor (NGF) expressions in PMC, vlPAG, and MPA regions in the brain. Wistar rats were used for the present study. The rats split into four groups; 4 groups (n = 6) in control group, BPH-induced group, BPH-induced and P. ginseng-treated group, and BPH-induced and finasteride-treated group. BPH in rats was induced by testosterone and the animals were evaluated for NGF expression in PMC, vlPAG, and MPA regions in the brain. The NGF expression was identified using immunohistochemistry (IHC). The NGF expression by IHC showed spots with dark brown color. In our results, NGF expressions in PMC, vlPAG, and MPA regions in the brainstem of the BPH-induced group showed increase than the control animal. These increased NGF expressions in three regions were decreased using treatment with P. ginseng (200 mg/kg). These results suggest that P. ginseng has therapeutic effects on the symptoms of BPH and is associated with the regulation of NGF expression in the brain. In conclusion, the administration of P. ginseng helps nerve growth factor activation.


The WISTAH hand study: a prospective cohort study of distal upper extremity musculoskeletal disorders.
Few prospective cohort studies of distal upper extremity musculoskeletal disorders have been performed. Past studies have provided somewhat conflicting evidence for occupational risk factors and have largely reported data without adjustments for many personal and psychosocial factors. A multi-center prospective cohort study was incepted to quantify risk factors for distal upper extremity musculoskeletal disorders and potentially develop improved methods for analyzing jobs. Disorders to analyze included carpal tunnel syndrome, lateral epicondylalgia, medial epicondylalgia, trigger digit, deQuervain's stenosing tenosynovitis and other tendinoses. Workers have thus far been enrolled from 17 different employment settings in 3 diverse US states and performed widely varying work. At baseline, workers undergo laptop administered questionnaires, structured interviews, two standardized physical examinations and nerve conduction studies to ascertain demographic, medical history, psychosocial factors and current musculoskeletal disorders. All workers' jobs are individually measured for physical factors and are videotaped. Workers are followed monthly for the development of musculoskeletal disorders. Repeat nerve conduction studies are performed for those with symptoms of tingling and numbness in the prior six months. Changes in jobs necessitate re-measure and re-videotaping of job physical factors. Case definitions have been established. Point prevalence of carpal tunnel syndrome is a combination of paraesthesias in at least two median nerve-served digits plus an abnormal nerve conduction study at baseline. The lifetime cumulative incidence of carpal tunnel syndrome will also include those with a past history of carpal tunnel syndrome. Incident cases will exclude those with either a past history or prevalent cases at baseline. Statistical methods planned include survival analyses and logistic regression. A prospective cohort study of distal upper extremity musculoskeletal disorders is underway and has successfully enrolled over 1,000 workers to date.


Band structures and band gaps of liquid surface waves propagating through an infinite array of cylinders.
The multiple scattering method is applied to the calculations of band structures of liquid surface waves propagating through an infinite array of vertical cylinders. The influence of the filling fraction on the formation of band gaps is discussed. It is found that there exist complete band gaps for both the square and triangular arrays of cylinders.


Cardiopulmonary function during and after prolonged extracorporeal circulation with membrane oxygenators in dogs.
Prolonged veno-arterial partial extracorporeal circulation using membrane oxygenator was performed in 19 alert dogs. Investigations of alterations in the corpuscular elements of the blood during the perfusion showed 89 mg% as the highest value of free haemoglobin. A significant decrease in the platelet count during the first two hours of bypass to a value of about 100 000/mm3 was found. Measurements of lung and heart functions did not reveal any significant differences between the baseline values and those obtained after 24 hours' bypass and again after three months' observation. Microscopic examination of the lungs and hearts only showed moderate focal alveolar oedema in the dogs killed immediately after 24 hours' bypass. These alterations could be explained as a consequence of the extracorporeal circulation. No changes were found at the microscopic examination of the lungs and hearts three months later. By haemodilution technique, the dogs suffered from severe universal oedema after a few hours of bypass and the perfusion time in these experiments did not exceed 13 hours. The observation that 24 hours of partial veno-arterial bypass using membrane oxygenators in healthy dogs causes only minor changes in heart and lung function and in lung histology might explain the possibility of using such oxygenators in prolonged perfusions.


Kinetic and Conformational Insights into Islet Amyloid Polypeptide Self-Assembly Using a Biarsenical Fluorogenic Probe.
Amyloid fibril formation and tissue deposition are associated with many diseases. Studies have shown that prefibrillar intermediates, such as oligomers, are the most toxic proteospecies of the amyloidogenic cascade. Thus, understanding the mechanisms of formation and the conformational ensemble of prefibrillar species is critical. Due to their transient and heterogeneous nature, detection and characterization of prefibrillar species remain challenging. The fluorogenic probe fluorescein arsenical hairpin (FlAsH), which recognizes a tetracysteine motif, has been recently used to detect the oligomerization of amyloidogenic peptides encompassing a Cys-Cys tag. In this study, we extended the FlAsH detection method to gain novel kinetic and conformational insights into the self-assembly of islet amyloid polypeptide (IAPP), a 37-residue peptide hormone whose deposition is associated with type II diabetes. By positional scanning of the Cys-Cys motif, the stability of the noncontiguous tetracysteine FlAsH-binding sites formed during self-assembly was evaluated and revealed rapid monomer self-recognition through the convergence of C-terminal domains. On the other hand, the N-terminal domains come close to each other only upon the formation of the cross-β-sheet amyloid structure. We demonstrated that this method is well-suited to detect thioflavin T-negative fibrils and to screen inhibitors of amyloid formation. This study highlights that with positional scanning of the split-tetracysteine motif (Cys-Cys), the FlAsH detection method offers unique time-dependent conformational insights on the proteospecies assembled throughout the amyloidogenic pathway.


Different presentations of intraretinal fluid collections in optic disc pits: OCT study of 3 cases.
The congenital optic disc pit is a rare anomaly that can lead to major visual impairment associated with subretinal fluid accumulation. The authors describe the optical coherence tomography study of three cases of untreated congenital optic disc pits with different levels of visual impairment and its different presentations of intraretinal fluid collections.


Cyclic thrombocytopenia related to menstrual cycle: a case report and literature review.
Cyclic thrombocytopenia (CTP) is rarely seen and characterized by periodic fluctuations in platelet counts. In some cases, it occurs in phase with menstrual cycle. A 40-year-old female, presented firstly on June 30, 2012, with a 40-day history of appearance of purpuric skin rash and bruising, was readmitted on Aug 14, when she noted bruise on her lips. The platelet count was 24×10(9)/L on June 30, 32×10(9)/L on Aug 14, while it was 161×10(9)/L on July 1, 110×10(9)/L on Aug 16. Physical examination show skin purpuric spots and bruise over the limbs and truck. Liver, spleen, lymph nodes were not enlarged. Antinuclear antibody and rheumatoid factor (RF) were positive. Results of immune complex levels, serum complements, Hp antibody and Thrombopoietin (TPO) were all within normal ranges. Bone marrow aspiration and biopsy shown there was no change in megakaryocyte number. Fluorescence-activated cell sorter (FACS) performed normal. JAK2-V617F gene mutational and platelet-associated antibodies were not detected. We observed the patient over two complete cycles, and continued investigating her blood counts for six months follow up. During the entire process, her menstrual was regular without heavy blood loss and prolonged period. Her hemoglobin and white cell counts remained normal without cyclic change. Even if the patient was not on any therapy designed to increase the platelet count, her platelet level was back to normal. Follow up to December, 2012; her platelet count continued to fluctuation, 20×10(9)/L-40×10(9)/L in the middle of menstrual cycle while 105×10(9)/L-197×10(9)/L at the menses.


Evaluation of the efficacy of Grofactor, a beta-adrenergic agonist based on zilpaterol hydrochloride, using feedlot finishing bulls.
Beta-adrenergic agonists (β-AA) have been shown to positively impact finishing performance and some carcass traits of feedlot cattle. Our objective was to evaluate the efficacy of a β-AA on the basis of zilpaterol hydrochloride (Grofactor, Laboratorios Virbac México, Guadalajara, Mexico) on growth and DMI, carcass characteristics, and meat quality of finishing bulls. Forty-five bulls (75% 25% ) initially weighing 448.7 ± 2.58 kg were blocked by BW and randomly assigned to 1 of 3 diets, using pens of 3 animals, in a randomized complete block design: 1) daily feeding without β-AA in the basal diet (Control), 2) daily feeding with 0.15 mg/kg BW of Grofactor added to the basal diet (ZHG), or 3) daily feeding with 0.15 mg/kg BW of Zilmax (MSD Salud Animal México, Mexico City, Mexico) added to the basal diet (ZHZ). The duration of the feeding period was 30 d with a subsequent 4-d withdrawal period. Compared with Control bulls, the group fed ZHG had a 12% better ( < 0.025) G:F ratio, and their final BW ( 0.094) and ADG ( 0.084) tended to be enhanced. Feedlot performance of ZHG and ZHZ bulls was similar, although the DMI was ∼4% lower ( 0.05) in ZHG bulls vs. the ZHZ and Control groups. The HCW ( 0.001) and dressing percentage ( 0.015) were higher by 20 kg and 3%, respectively, in ZHG bulls vs. Control bulls. The KPH fat was lower ( 0.007) in bulls fed ZHG than in nonsupplemented bulls, but other carcass characteristics were not different in the ZHG and ZHZ bulls, and noncarcass components were not affected by ZHG or ZHZ supplementation. At 48 h postmortem, ZHG bulls had lower ( 0.007) water holding capacity and trended toward ( 0.06) increased chroma and reduced pH ( 0.09) compared to Control bulls. However, compared to ZHZ bulls, ZHG bulls had higher ( 0.02) chroma and a trend ( 0.08) toward increased hue angle. At 14 d postmortem, meat quality variables did not differ between the 3 groups of bulls. Supplementation of ZH Grofactor improved feedlot performance and some carcass characteristics of finishing bulls without affecting meat quality. The effects of Grofactor on feedlot performance, carcass traits, and meat quality were similar to those of Zilmax.


Effects of experimentally induced panic attacks on neuroimmunological markers.
Since little is known concerning regulation of immunological parameters in rapid changing psychiatric states like panic attacks, we measured cytokines at different time points in healthy subjects, which underwent experimental panic induction using the CCK-4 paradigm. Apart from a challenge related IL-6 increase, we could not observe any changes of neuroimmunological markers in relation to acute anxiety with regard to time and group. Herein we conducted for the first time a new approach to immunological research in panic disorder, suggesting immune changes are more related to long term disease stress.


Presence of Human Hepegivirus-1 in a Cohort of People Who Inject Drugs.
Next-generation metagenomic sequencing (NGMS) has opened new frontiers in microbial discovery but has been clinically characterized in only a few settings. To explore the plasma virome of persons who inject drugs and to characterize the sensitivity and accuracy of NGMS compared with quantitative clinical standards. Longitudinal and cross-sectional studies. A clinical trial (ClinicalTrials.gov: NCT01285050) and a well-characterized cohort study of persons who have injected drugs. Persons co-infected with hepatitis C virus (HCV) and HIV. Viral nucleic acid in plasma by NGMS and quantitative polymerase chain reaction (PCR). Next-generation metagenomic sequencing generated a total of 600 million reads, which included the expected HIV and HCV RNA sequences. HIV and HCV reads were consistently identified only when samples contained more than 10 000 copies/mL or IU/mL, respectively, as determined by quantitative PCR. A novel RNA virus, human hepegivirus-1 (HHpgV-1), was also detected by NGMS in 4 samples from 2 persons in the clinical trial. Through use of a quantitative PCR assay for HHpgV-1, infection was also detected in 17 (10.9%) of 156 members of a cohort of persons who injected drugs. In these persons, HHpgV-1 viremia persisted for a median of at least 4538 days and was associated with detection of other bloodborne viruses, such as HCV RNA and SEN virus D. The medical importance of HHpgV-1 infection is unknown. Although NGMS is insensitive for detection of viruses with relatively low plasma nucleic acid concentrations, it may have broad potential for discovery of new viral infections of possible medical importance, such as HHpgV-1. National Institutes of Health.


Impact of voice- and knowledge-enabled clinical reporting--US example.
This study shows qualitative and quantitative estimates of the national and the clinic level impact of utilizing voice and knowledge enabled clinical reporting systems. Using common sense estimation methodology, we show that the delivery of health care can experience a dramatic improvement in four areas as a result of the broad use of voice and knowledge enabled clinical reporting: (1) Process Quality as measured by cost savings, (2) Organizational Quality as measured by compliance, (3) Clinical Quality as measured by clinical outcomes and (4) Service Quality as measured by patient satisfaction. If only 15 percent of US physicians replaced transcription with modem clinical reporting voice-based methodology, about one half billion dollars could be saved. $6.7 Billion could be saved annually if all medical reporting currently transcribed was handled with voice-and knowledge-enabled dictation and reporting systems.


Hepatic clearance models: comparison of the dispersion and Goresky models in outflow profiles from multiple indicator dilution rat liver studies.
The multiple indicator dilution (MID) technique is often used for investigation of the kinetic behavior of substrates and metabolites in eliminating organs. The present study was a systematic comparison of the utility of the Goresky model (GM) (a structural model) and the mixed-boundary dispersion model (DM) (a stochastic model) in the interpretation of influx, efflux, and removal (sequestration) coefficients, with data generated from rat liver-perfusion/MID studies. Although the GM and the DM are equivalent in their descriptions of membrane transport, they differ in their classifications of the dispersion of blood-borne elements. For the DM, the dispersion is an inverse Gaussian distribution of vascular transit times; for the GM, it is accounted for by the dispersion observed among noneliminated reference indicators (e.g. labeled red blood cells, albumin, sucrose, and H2O) or the derived reference. In this study, previously published rat liver-perfusion/MID data obtained for the glutathione conjugate of bromosulfophthalein and hippuric acid, compounds that exhibit saturable carrier-mediated transport, with the GM were reanalyzed with the two-compartment DM. When the fitted values for volume and transfer coefficients were compared, good correlation was found between the fitted vascular volume for the DM and the vascular volume for the reference indicator for the GM. The influx coefficients were generally similar between the models, but improved correspondence was observed when the DM was modified to include the large-vessel transit time. In contrast, the efflux and sequestration coefficients obtained for the DM did not correspond well to those from the GM. The disagreement was due, in part, to differences in the interpretation of the late-in-time component of the reference transit time distribution curve, which was not described well by the DM. Consequently, the residence time distribution and the relative dispersion were underestimated by the DM.


Mechanisms of protein-folding diseases at a glance.
For a protein to function appropriately, it must first achieve its proper conformation and location within the crowded environment inside the cell. Multiple chaperone systems are required to fold proteins correctly. In addition, degradation pathways participate by destroying improperly folded proteins. The intricacy of this multisystem process provides many opportunities for error. Furthermore, mutations cause misfolded, nonfunctional forms of proteins to accumulate. As a result, many pathological conditions are fundamentally rooted in the protein-folding problem that all cells must solve to maintain their function and integrity. Here, to illustrate the breadth of this phenomenon, we describe five examples of protein-misfolding events that can lead to disease: improper degradation, mislocalization, dominant-negative mutations, structural alterations that establish novel toxic functions, and amyloid accumulation. In each case, we will highlight current therapeutic options for battling such diseases.


Extracting optical constants of solid materials with micro-rough surfaces from ellipsometry without using effective medium approximation.
The effective medium approximation (EMA) model may cause a large deviation in the data analysis of spectroscopic ellipsometry (SE) for solid materials with randomly micro-rough surfaces since it ignores the influence of the lateral irregularities of the rough surfaces on the electromagnetic scattering. In this work, a novel inversion framework is developed to extract optical constants from the SE parameters for solid materials with randomly micro-rough surfaces. Our approach enables the integration of the Levenberg-Marquardt optimization algorithm and the first-principles calculations of electromagnetic scattering. In each iterative step, the electromagnetic interactions with rough surfaces are accurately obtained from first-principles calculations without using the EMA model for rough estimation, which significantly guarantees the precision and wide applicability of our method for actual surfaces without a perfectly Gaussian height distribution. Furthermore, a superior advantage of our approach is that its error can be feasibly evaluated from the instrumental errors of the surface morphology detectors and the SE.


Comparative densities of Wuchereria bancrofti microfilaria in paired samples of capillary and venous blood.
Concurrent finger-prick and venous blood samples were obtained from 43 patients infected with Wuchereria bancrofti. Microfilariae were counted in blood smears and on nuclepore filters. Based on the numbers of microfilariae in 20-microliters finger-prick samples, an expected (theoretical) number of microfilariae in venous samples was calculated. This expected value was compared to the actual number of microfilariae present in venous blood. The actual number of microfilariae present ranged from 0.7 to 30 times (median 3) less than expected. The exponential function y = 16.74e.17x, r2 = .69, where y = venous counts and x = capillary counts was found to accurately reflect the relationship between venous and capillary counts. Each unit (microfilaria) change in capillary blood would result in an expected 19% unit increase/decrease in venous blood. The results support strongly the theory that microfilariae are unevenly distributed in the blood system. The epidemiological implication is that persons with low or ultralow microfilaremia levels in venous blood may have a much greater pool of microfilaria available in capillaries. We believe that the present study explains, at least partially, why mosquitoes feeding on these kinds of microfilaria carriers (frequently) have a greater uptake fo microfilariae than expected.


Human B lymphocyte function: cell triggering and immunoregulation.
Several recent developments in human immunobiology have resulted in significant advances in our understanding of the complex processes involved in activation and immunoregulation of function in human B lymphocytes in normal and disease states. The development of antigen-specific systems for the study of B-cell function has allowed a dissection of the dichotomy and overlap between specificity and polyclonality of responses that are so clearly manifested in certain infectious and autoimmune diseases. In addition, the development of antigen-specific T-cell clones has led to a clear-cut understanding of the cellular and genetic requirements for the induction and regulation of human immune responses. Most recently, B-cell hybrids secreting human monoclonal antibodies with predetermined antigenic specificities have been developed from peripheral blood B cells of immunized individuals. Monoclonal antibodies should allow for the availability of unlimited quantities of purified human antibody specific to relevant antigens for diagnostic and therapeutic purposes.


Xe nuclear magnetic resonance line shapes in channels decorated with paramagnetic centers.
To make predictions of the Xe NMR line shapes for Xe in channels decorated with paramagnetic centers, we consider a model system using the O(2) molecule as the paramagnetic center. The previously calculated quantum mechanical Xe@O(2) hyperfine tensor for various configurations of Xe in the presence of O(2) provides a model for the hyperfine response of Xe atom to the presence of a paramagnetic center. The averaging is carried out using the same grand canonical Monte Carlo methodology as for calculating NMR line shapes for Xe in diamagnetic channels, modified to include the effects of the hyperfine tensor response. We explore the temperature dependence of the Xe line shapes, the dependence on the concentration, and the symmetry of distribution of embedded paramagnetic centers, on the orientation of the paramagnetic center axis with respect to the channel axis, and on the radial distance of the paramagnetic center from the axis of the channel. We predict Xe line shape signatures of the presence and orientation of paramagnetic centers and deduce which tensor elements provide measures of concentration and radial distance of paramagnetic centers from the channel axis.


Bioactive peptides in the pancreatin-hydrolysates of whey protein support cell proliferation and scavenge reactive oxygen species.
Whey protein (WP) in milk shows physiologically active functions such as cholesterol control and immune system strengthening. In this study, we performed hydrolysis and peptide polarity fractionation to enhance the efficacy and diversity of its physiological activities, using the digesting enzyme, pancreatin. Our results indicate that hydrolysis significantly increased the cell proliferation of the WP fractions, with the lower-polarity fractions showing greater efficacy in this regard. Our results indicate that hydrolysis significantly increases cell proliferation of the WP fractions. Additionally, we confirmed differences in the antioxidant activity of the WP fractions as a function of polarity was confirmed via scavenging 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay in vitro. WP itself did not show anti-inflammatory efficacy. However, all the hydrolyzed fractions downregulated the mRNA expression levels of inflammatory cytokines in all treated cell lines and, based on a senescence-associated (SA)-β-galactosidase assay, the fraction with the lowest polarity (F6) inhibited cellular senescence to the greatest extent. Furthermore, we identified the peptide sequences with various physiological activities from whey protein hydrolysates through mass spectrometry. Taken together, our results indicate that the fractionation of WP via hydrolysis generates novel functions including promoting cellular cell proliferation, anti-inflammatory effects, and enhancing antioxidant and anti-cellular senescence.


Oxidative N-dealkylation reactions by oxoiron(IV) complexes of nonheme and heme ligands.
Nonheme and heme iron monooxygenases participate in oxidative N-dealkylation reactions in nature, and high-valent oxoiron(IV) species have been invoked as active oxidants that effect the oxygenation of organic substrates. The present study describes the first example of the oxidative N-dealkylation of N,N-dialkylamines by synthetic nonheme oxoiron(IV) complexes and the reactivity comparisons of nonheme and heme oxoiron(IV) complexes. Detailed mechanistic studies were performed with various N,N-dialkylaniline substrates such as para-substituted N,N-dimethylanilines, para-chloro-N-ethyl-N-methylaniline, para-chloro-N-cyclopropyl-N-isopropylaniline, and deuteriated N,N-dimethylanilines. The results of a linear free-energy correlation, inter- and intramolecular kinetic isotope effects, and product analysis studied with the mechanistic probes demonstrate that the oxidative N-dealkylation reactions by nonheme and heme oxoiron(IV) complexes occur via an electron transfer-proton transfer (ET-PT) mechanism.


eNewborn: The Information Technology Revolution and Challenges for Neonatal Networks.
Among preterm infants, 1-2% are born before 32 weeks of gestation or have a birth weight below 1,500 g. They contribute disproportionately to the burden of mortality and morbidity related to preterm birth, whether in the neonatal period or later in life. They are the target population studied in neonatal networks. Improving neonatal care and later outcome is a major issue in public health. Neonatologists, health care providers, public authorities, parents and families, industry, and all organizations dedicated to infant health must bring their efforts together and dedicate their actions in order to do so. Neonatal networks are the strongest platforms through which to achieve this goal. The progressive information technology (IT) revolution is leading to a new approach. The power of search engines and new technological devices opens extraordinary new perspectives in terms of speed, storing, sharing, and innovative approaches in providing health care. However, difficulties are expected with old applications that cannot evolve in the new IT environment. Security and privacy in data collection are future challenges to be addressed. Here, we describe the eNewborn project and its original software. The main functionalities are interactive navigation, harmonization with other formats, linkage with other databases, and strict security and privacy procedures.


Gene therapy for prostate cancer delivered by ovine adenovirus and mediated by purine nucleoside phosphorylase and fludarabine in mouse models.
A gene-directed enzyme pro-drug therapy (GDEPT) based on purine nucleoside phosphorylase (PNP), that converts the prodrug, fludarabine to 2-fluoroadenine, has been described, but studies are limited compared with other GDEPTs. We investigated the in vitro and in vivo efficacies of PNP-GDEPT for treating androgen-independent (AI) prostate cancer. The PNP gene controlled by Rous sarcoma virus (RSV) constitutive promoter was delivered using a recombinant ovine adenovirus vector (OAdV220) that uses a different receptor from human adenovirus type 5. In vitro, OAdV220 provided increased transgene expression over a comparable human Ad5 vector in infected AI, murine RM1 prostate cancer cells. Subsequent in vivo testing was therefore confined to OAdV220. Transduction of RM1 cells with OAdV220 before implantation in immunocompetent mice dramatically inhibited subcutaneous (s.c.) tumor growth when fludarabine phosphate was administered systemically and increased mouse survival in a dose-dependent manner. In tumor-bearing C57BL/6 mice, a single intratumoral injection of OAdV220 produced detectable PNP activity for at least 6 days and with prodrug, retarded the growth of aggressive RM1 s.c. tumors by 35% at day 14. There was a consistent trend to reduction of pre-established intraprostatic RM1 tumors. A similar regimen induced significant therapeutic efficacy in human PC3 xenografts. Thus, ovine adenovirus-mediated GDEPT using the PNP system was effective in vivo against AI prostate cancers, the aggressive murine RM1, and the human PC3 lines. Methods that improve viral dissemination and stimulate the immune system in vivo may further improve efficacy.


Supporting School Mental Health Providers: Evidence from a Short-Term Telementoring Model.
To support student mental health, school staff must have knowledge of evidence-based practices and the capacity to implement them. One approach used to address this challenge is a group-based telementoring model called Extension for Community Healthcare Outcomes (ECHO). In other applications (e.g., healthcare settings), ECHO has been shown to increase healthcare professionals' self-efficacy and knowledge of evidence-based practices leading to improved patient outcomes. This study examined the potential for ECHO to be used as a method for increasing school staff engagement and knowledge of evidence-based school mental health practices. Using a quasi-experimental design, this study compared outcomes across two professional development experiences aimed at promoting school staff ability to provide evidence-based mental health services. School staff from four school districts participated in a school mental health training initiative. All participants (N = 57) had access to asynchronous, online mental health modules. A sub-sample (n = 33) was also offered monthly ECHO sessions. Tests of group difference in outcomes revealed significant increases in engagement with online learning (d = 0.58) and satisfaction (d = 0.82) for those who participated in ECHO as compared to those who did not. Knowledge about evidence-based practices was not significantly different between groups. Results suggest that group-based telementoring may be a promising approach for improving engagement and satisfaction with training initiatives aimed at promoting evidence-based school mental health practices. However, further study of ProjectECHO using experimental designs is needed to make causal inferences about its effect on provider outcomes.


Concentrations of soluble Fas and soluble Fas ligand as indicators of programmed cell death among patients coinfected with Human Immunodeficiency Virus and Hepatitis C Virus.
Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) coinfections can affect mechanisms of programmed cell death and therefore influence acquired immunodeficiency syndrome (AIDS) development as well as the course of chronic hepatitis C. The aim of the study was to assess soluble Fas (sFas) and soluble Fas ligand (sFasL) concentrations in HIV- and HCV-coinfected patients and, moreover, to establish their relationships with HIV viral load, CD4+ T lymphocyte count, as well as liver function tests. Seventy-eight patients were included in the study, among them 30 coinfected with HIV and HCV, 10 infected only with HIV, and 38 infected only with HCV. HIV infection was confirmed by means of Western blot analysis; HIV viral load was measured by RTPCR; and CD3+, CD4+, and CD8+ T lymphocyte counts were established by means of flow cytometry. HCV infection was confirmed through HCV RNA isolation, using RT-PCR. sFas and sFasL concentrations were measured in duplicate by ELISA. The mean CD4+ T lymphocyte count decreased in HIV- and HCV-coinfected patients versus HIV-infected individuals (429 versus 279/ml). sFasL protein was detectable principally in HIV-infected individuals without HCV infection (90%), whereas in those with HCV infection it occurred only in 11% of cases. The highest sFas concentration was observed in HCV-infected patients (25.9 ng/ml) as well as in HIV- and HCV-coinfected individuals (20.3 ng/ml). This concentration was negatively proportional to sFasL prevalence. The results of our study suggest that HCV infection in HIV-positive individuals may suppress processes of programmed cell death. There was no correlation between sFas, sFasL, and HIV-1 viral load. On the other hand, sFas concentration and the presence of sFasL were related to CD4+ T lymphocyte count.


External validation of cardiac arrest-specific prognostication scores developed for early prognosis estimation after out-of-hospital cardiac arrest in a Korean multicenter cohort.
We evaluated the performance of cardiac arrest-specific prognostication scores developed for outcome prediction in the early hours after out-of-hospital cardiac arrest (OHCA) in predicting long-term outcomes using independent data. The following scores were calculated for 1,163 OHCA patients who were treated with targeted temperature management (TTM) at 21 hospitals in South Korea: OHCA, cardiac arrest hospital prognosis (CAHP), C-GRApH (named on the basis of its variables), TTM risk, 5-R, NULL-PLEASE (named on the basis of its variables), Serbian quality of life long-term (SR-QOLl), cardiac arrest survival, revised post-cardiac arrest syndrome for therapeutic hypothermia (rCAST), Polish hypothermia registry (PHR) risk, and PROgnostication using LOGistic regression model for Unselected adult cardiac arrest patients in the Early stages (PROLOGUE) scores and prediction score by Aschauer et al. Their accuracies in predicting poor outcome at 6 months after OHCA were determined using the area under the receiver operating characteristic curve (AUC) and calibration belt. In the complete-case analyses, the PROLOGUE score showed the highest AUC (0.923; 95% confidence interval [CI], 0.904-0.941), whereas the SR-QOLl score had the lowest AUC (0.749; 95% CI, 0.711-0.786). The discrimination performances were similar in the analyses after multiple imputation. The PROLOGUE, TTM risk, CAHP, NULL-PLEASE, 5-R, and cardiac arrest survival scores were well calibrated. The rCAST and PHR risk scores showed acceptable overall calibration, although they showed miscalibration under the 80% CI level at extreme prediction values. The OHCA score, C-GRApH score, prediction score by Aschauer et al., and SR-QOLl score showed significant miscalibration in both complete-case (P = 0.026, 0.013, 0.005, and < 0.001, respectively) and multiple-imputation analyses (P = 0.007, 0.018, < 0.001, and < 0.001, respectively). In conclusion, the discrimination performances of the prognostication scores were all acceptable, but some showed significant miscalibration.


Inhaler Errors in the CRITIKAL Study: Type, Frequency, and Association with Asthma Outcomes.
Poor inhaler technique has been linked to poor asthma outcomes. Training can reduce the number of inhaler errors, but it is unknown which errors have the greatest impact on asthma outcomes. The CRITical Inhaler mistaKes and Asthma controL study investigated the association between specific inhaler errors and asthma outcomes. This analysis used data from the iHARP asthma review service-a multicenter cross-sectional study of adults with asthma. The review took place between 2011 and 2014 and captured data from more than 5000 patients on demographic characteristics, asthma symptoms, and inhaler errors observed by purposefully trained health care professionals. People with asthma receiving a fixed-dose combination treatment with inhaled corticosteroids and long-acting beta agonist were categorized by the controller inhaler device they used-dry-powder inhalers or metered-dose inhalers: inhaler errors were analyzed within device cohorts. Error frequency, asthma symptom control, and exacerbation rate were analyzed to identify critical errors. This report contains data from 3660 patients. Insufficient inspiratory effort was common (made by 32%-38% of dry-powder inhaler users) and was associated with uncontrolled asthma (adjusted odds ratios [95% CI], 1.30 [1.08-1.57] and 1.56 [1.17-2.07] in those using Turbohaler and Diskus devices, respectively) and increased exacerbation rate. In metered-dose inhaler users, actuation before inhalation (24.9% of patients) was associated with uncontrolled asthma (1.55 [1.11-2.16]). Several more generic and device-specific errors were also identified as critical. Specific inhaler errors have been identified as critical errors, evidenced by frequency and association with asthma outcomes. Asthma management should target inhaler training to reduce key critical errors.


An investigation of the added value of an ACPA multiplex assay in an early rheumatoid arthritis setting.
Recently, arrays have become available that allow the simultaneous analysis of several anti-citrullinated protein antibody (ACPA) reactivities using distinct citrullinated peptides. Such assays are designed for exploratory studies. The interpretation of positive antibody reactivities can best be made if the diagnostic and prognostic value of a multiplex array in an early arthritis setting is known and if the multiplex-positive patients who are negative according to three commonly used commercial ACPA assays are characterized. Using Thermo Scientific's ImmunoCap ISAC (Immuno Solid-phase Allergen Chip) system, a multiplexed array that determines reactivities to 11 citrullinated peptides, we analysed serum/plasma of 195 healthy controls and 1282 early arthritis patients from two independent cohorts: the Leiden Early Arthritis Clinic (n = 1013) and the IMPROVED (n = 269) cohort. Findings were compared with results primarily of the anti-citrullinated cyclic peptide 2 (anti-CCP-2) assay but also with anti- CCP-3 and anti-mutated citrullinated vimentin (anti-MCV) assays. The associations between ACPA reactivities and patient characteristics, risk factors (shared epitope, smoking) and disease outcomes (progression of undifferentiated arthritis to rheumatoid arthritis (RA) and severity of joint destruction) were assessed. Thirty-one percent of anti-CCP-2-negative RA patients displayed reactivity toward citrullinated peptides in the multiplex assay. These patients had a positive signal toward a more restricted peptide repertoire than anti-CCP-2-positive RA patients (median of 1 versus 5). Within anti-CCP-2-negative patients, ACPA reactivity as detected by multiplex array was not significantly associated with known risk factors or clinical or prognostic parameters. The frequency of sera from anti-CCP-2-negative RA patients who were positive for the multiplexed peptides was comparable to the frequency in non-RA arthritic patients (27 %). Additive citrulline peptide reactivities detected by the current multiplex system did not reach significant power to be RA-specific. The presence of residual citrulline reactivities detected by this multiplex system in arthritis patients who are negative in commercial ACPA assays needs to be interpreted with caution.


Sarcocystis dubeyi n. sp. (Protozoa: Sarcocystidae) in the water buffalo (Bubalus bubalis).
Sarcocystis dubeyi n. sp. is proposed for a species forming thick-walled, microscopic sarcocysts in striated muscular tissues of the water buffalo (Bubalus bubalis). Sarcocysts of S. dubeyi were found in histological sections of skeletal muscles and esophagus, but not in heart and tongue, of 8 (13%) of 60 water buffaloes examined in Ho Chi Minh City, Vietnam. Sarcocysts of S. dubeyi were up to 600 microns long and up to 200 microns wide. The cyst wall was 4.5-9 microns thick and was composed of tightly packed, cylindrical villar protrusions (Vp) that had a uniform width of up to 3 microns, a length of up to 8 microns, and a blunt, often flattened tip. The Vp contained microfilaments but no prominent electron-dense granules. The definitive host of S. dubeyi was not determined, but it could possibly be humans or other primates. By the present description, 4 Sarcocystis species are recognized in the water buffalo: the macrocyst-forming Sarcocystis fusiformis and S. buffalonis and the microcyst-forming S. levinei and S. dubeyi.


Estimation of virological and immunological parameters in subjects from South India infected with human immunodeficiency virus type 1 clade C and correlation of findings with occurrence of neurological disease.
Several studies carried out in Western countries have demonstrated that a number of virological and immunological markers such as viral loads, cytokines, beta(2)-microglobulin, neopterin, etc., are elevated in the serum and cerebrospinal fluid (CSF) of human immunodeficiency virus (HIV)-infected individuals with neurological disease. The neurological manifestations of HIV infection noted in Indian patients is different from those reported in Western countries. Moreover, few studies have investigated the role of virological and immunological parameters with respect to the progression of HIV-1 clade C infection in India. In this study, we measured virological (HIV-1 RNA levels) and immunological parameters (CD4 cell count and inflammatory markers) in the plasma and CSF of HIV-1-infected neurologically asymptomatic and symptomatic (with opportunistic infections and/or dementia) subjects. By using clade-specific polymerase chain reaction (PCR), we ascertained that all samples used for the study were infected with HIV-1 clade C. Among the various laboratory parameters evaluated, high viral loads in the CSF, low CD4 counts, and higher levels of interleukin (IL)-1alpha, IL-6, tumor necrosis factor alpha (TNFalpha), beta(2)-microglobulin, and neopterin were noted in HIV-infected subjects with neurological disease as compared to asymptomatic subjects. These data suggest that the markers evaluated in plasma and CSF samples correlated with occurrence of neurological disease in symptomatic individuals as compared to asymptomatic HIV infected subjects.


Five birds, one stone: neutralization of α-hemolysin and 4 bi-component leukocidins of Staphylococcus aureus with a single human monoclonal antibody.
Staphylococcus aureus is a major human pathogen associated with high mortality. The emergence of antibiotic resistance and the inability of antibiotics to counteract bacterial cytotoxins involved in the pathogenesis of S. aureus call for novel therapeutic approaches, such as passive immunization with monoclonal antibodies (mAbs). The complexity of staphylococcal pathogenesis and past failures with single mAb products represent considerable barriers for antibody-based therapeutics. Over the past few years, efforts have focused on neutralizing α-hemolysin. Recent findings suggest that the concerted actions of several cytotoxins, including the bi-component leukocidins play important roles in staphylococcal pathogenesis. Therefore, we aimed to isolate mAbs that bind to multiple cytolysins by employing high diversity human IgG1 libraries presented on the surface of yeast cells. Here we describe cross-reactive antibodies with picomolar affinity for α-hemolysin and 4 different bi-component leukocidins that share only ∼26% overall amino acid sequence identity. The molecular basis of cross-reactivity is the recognition of a conformational epitope shared by α-hemolysin and F-components of gamma-hemolysin (HlgAB and HlgCB), LukED and LukSF (Panton-Valentine Leukocidin). The amino acids predicted to form the epitope are conserved and known to be important for cytotoxic activity. We found that a single cross-reactive antibody prevented lysis of human phagocytes, epithelial and red blood cells induced by α-hemolysin and leukocidins in vitro, and therefore had superior effectiveness compared to α-hemolysin specific antibodies to protect from the combined cytolytic effect of secreted S. aureus toxins. Such mAb afforded high levels of protection in murine models of pneumonia and sepsis.


Self-care in heart failure patients.
to describe self-care behavior and its associated factors in a sample of heart failure Brazilian patients. descriptive cross-sectional study with non-probabilistic sample of 116 ambulatory patients undergoing heart failure treatment. Self-care was evaluated using the Self-Care of Heart Failure Index, (scores ≥70 points=appropriate self-care). Association tests were applied, considering a descriptive level of 0.05. the mean age of participants was 57.7 (SD =11.3) years; 54.3% were male; the mean schooling was 5.5 (SD = 4.0) years; and 74.1% had functional class II-III. The mean scores on the subscales of the Self-Care of Heart Failure Index indicated inappropriate self-care (self-care maintenance: 53.2 (SD =14.3), selfcare management: 50.0 (SD = 20.3) and self-care confidence: 52.6 (SD=22.7)) and it was found low frequencies of participants with appropriate self-care (self-care maintenance, 6.9%), self-care management (14.7%) and self-care confidence (19%). Higher scores of the Self-Care of Heart Failure Index were associated with: reduced left ventricular ejection fraction (p=0.001), longer time of experience with the disease (p=0.05) and joint monitoring by physician and nurse (p=0.007). investments are needed to improve the self-care behavior and the nursing can play a relevant role in this improvement.


Comparison of depth cameras for three-dimensional reconstruction in medicine.
KinectFusion is a typical three-dimensional reconstruction technique which enables generation of individual three-dimensional human models from consumer depth cameras for understanding body shapes. The aim of this study was to compare three-dimensional reconstruction results obtained using KinectFusion from data collected with two different types of depth camera (time-of-flight and stereoscopic cameras) and compare these results with those of a commercial three-dimensional scanning system to determine which type of depth camera gives improved reconstruction. Torso mannequins and machined aluminium cylinders were used as the test objects for this study. Two depth cameras, Microsoft Kinect V2 and Intel Realsense D435, were selected as the representatives of time-of-flight and stereoscopic cameras, respectively, to capture scan data for the reconstruction of three-dimensional point clouds by KinectFusion techniques. The results showed that both time-of-flight and stereoscopic cameras, using the developed rotating camera rig, provided repeatable body scanning data with minimal operator-induced error. However, the time-of-flight camera generated more accurate three-dimensional point clouds than the stereoscopic sensor. Thus, this suggests that applications requiring the generation of accurate three-dimensional human models by KinectFusion techniques should consider using a time-of-flight camera, such as the Microsoft Kinect V2, as the image capturing sensor.


Structure and vibrational spectroscopy of methanesulfonic acid.
In this work, we have used a combination of vibrational spectroscopy (infrared, Raman and inelastic neutron scattering) and periodic density functional theory to investigate the structure of methanesulfonic acid (MSA) in the liquid and solid states. The spectra clearly show that the hydrogen bonding is much stronger in the solid than the liquid state. The structure of MSA is not known; however, mineral acids typically adopt a chain structure in condensed phases. A periodic density functional theory (CASTEP) calculation based on the linear chain structure found in the closely related molecule trifluoromethanesulfonic acid gave good agreement between the observed and calculated spectra, particularly with regard to the methyl and sulfonate groups. The model accounts for the large widths of the asymmetric S-O stretch modes; however, the external mode region is not well described. Together, these observations suggest that the basic model of four molecules in the primitive unit cell, linked by hydrogen bonding into chains, is correct, but that MSA crystallizes in a different space group than that of trifluoromethanesulfonic acid.


Properties of the melatonin-generating system of the sailfin molly, Poecilia velifera.
The properties of the melatonin-generating system of a tropical teleost, the sailfin molly (Poecilia velifera), were investigated in vitro in a series of experiments using static or perifusion culture techniques. The properties examined included photic entrainment, circadian rhythmicity under continuous light (LL) and continuous darkness (DD), functionality of the melatonin-generating system at birth, and presence of multiple circadian oscillators in the molly pineal. Pineal glands or skull caps with the pineal gland firmly attached were dissected from adult and new-born fishes, respectively, and placed into static or perifusion culture at constant temperature (27 degrees C) depending upon the experiment. Melatonin release in samples was quantified by RIA. Rhythmic melatonin release was observed from isolated adult pineals under 12L:12D and 14L:10D, with low amounts of melatonin released during the light and high amounts during the dark. Melatonin release was inhibited by LL. However, under DD, melatonin release was robust and rhythmic with a circadian period (Tau) that ranged between 21.3 and 27.0 h (n = 21). Pineals from new-born (1-day old) mollies released melatonin rhythmically under a light:dark cycle and DD in both static and perifusion culture. Melatonin release from half and quarter pineals of adult mollies under DD was robust and rhythmic with circadian periods that ranged between 22.5 and 29.0 h (n = 19). Taken together, these data show that the molly pineal is photosensitive, fully functional from birth, and contains multiple circadian oscillators (at least four) regulating melatonin production.


An Ab Initio Correction Vector Restricted Active Space Approach to the L-Edge XAS and 2p3d RIXS Spectra of Transition Metal Complexes.
We describe an ab initio approach to simulate L-edge X-ray absorption (XAS) and 2p3d resonant inelastic X-ray scattering (RIXS) spectroscopies. We model the strongly correlated electronic structure within a restricted active space and employ a correction vector formulation instead of sum-over-state expressions for the spectra, thus eliminating the need to calculate a large number of intermediate and final electronic states. We present benchmark simulations of the XAS and RIXS spectra of the iron complexes [FeCl4]1-/2- and [Fe(SCH3)4]1-/2- and interpret the spectra by deconvolving the correction vectors. Our approach represents a step toward simulating the X-ray spectroscopies of larger metal cluster systems that play a pivotal role in biology.


Attenuated skin blood flow response to hyperthermia in paraplegic men.
To clarify how skin and internal temperatures interact in control of skin blood flow, five male paraplegic subjects (lesions at the level of thoracic vertebrae 1-11) (29-47 yr old) were heated in water-perfused suits to elevate oral temperature (To) 1-1.5 degrees C. In part I only the insensate skin was heated; sensate skin was kept at 32-34 degrees C. No appreciable elevation of forearm blood flow (FBF) or sweating occurred, even with To at 38 degrees C. In part II the suit was applied to the whole body so that skin temperature was 40 degrees C, except for one arm that remained at 32-34 degrees C for FBF measurement. Sweating was noted above the lesion in all but one subject. FBF increased in all subjects but was far below levels previously reported for hyperthermic normal men; also, thresholds appeared elevated. To the extent that effector connections are intact, attenuated FBF response implies that either 1) some vasoconstrictor bias associated with cardiovascular regulation is active or 2) thermoregulatory effector outflow is diminished. If the latter is true, it follows that the effector outflow reduction relates to diminished afferent input. But the component of the effector outflow contributed by peripheral thermoreception is small; thus these findings may indicate that what is lacking in the afferent input is central thermoreception from below the lesion, possibly from the spinal cord itself.


Dosimetric Effects of Magnetic Resonance Imaging-assisted Radiotherapy Planning: Dose Optimization for Target Volumes at High Risk and Analytic Radiobiological Dose Evaluation.
Based on the assumption that apparent diffusion coefficients (ADCs) define high-risk clinical target volume (aCTVHR) in high-grade glioma in a cellularity-dependent manner, the dosimetric effects of aCTVHR-targeted dose optimization were evaluated in two intensity-modulated radiation therapy (IMRT) plans. Diffusion-weighted magnetic resonance (MR) images and ADC maps were analyzed qualitatively and quantitatively to determine aCTVHR in a high-grade glioma with high cellularity. After confirming tumor malignancy using the average and minimum ADCs and ADC ratios, the aCTVHR with double- or triple-restricted water diffusion was defined on computed tomography images through image registration. Doses to the aCTVHR and CTV defined on T1-weighted MR images were optimized using a simultaneous integrated boost technique. The dosimetric benefits for CTVs and organs at risk (OARs) were compared using dose volume histograms and various biophysical indices in an ADC map-based IMRT (IMRTADC) plan and a conventional IMRT (IMRTconv) plan. The IMRTADC plan improved dose conformity up to 15 times, compared to the IMRTconv plan. It reduced the equivalent uniform doses in the visual system and brain stem by more than 10% and 16%, respectively. The ADC-based target differentiation and dose optimization may facilitate conformal dose distribution to the aCTVHR and OAR sparing in an IMRT plan.


Evaluation of the causes of sex disparity in heart failure trials.
Cardiovascular disease is one of the leading causes of mortality and morbidity in women. Despite this, even in contemporary research, female patients are poorly represented in trials. This study aimed to explore reasons behind the sex disparity in heart failure (HF) trials. HF trials published in seven high-impact clinical journals (impact factor >20), between 2000 and 2020, were identified. Trials with over 300 participants of both sexes were included. Large HF registries, as well as population statistics, were also identified using the same criteria. We identified 146 HF trials, which included 248 620 patients in total. The median proportion of female patients was 25.8%, with the lowest proportions seen in trials enrolling patients with ischaemic cardiomyopathy (17.9%), severe systolic dysfunction (left ventricular ejection fraction (LVEF) <35%) (21.4%) and those involving an invasive procedure (21.1%). The highest proportion of women was seen in trials assessing HF with preserved LVEF (51.6%), as well as trials including older participants (40.5%). Significant differences were seen between prevalence of female trial participants and population prevalence in all LVEF categories (25.8% vs 49.0%, p<0.01). A significant sex disparity was identified in HF trials, most visible in trials assessing patients with severely reduced LVEF and ischaemic aetiology. This is likely due to a complex interplay between enrolment bias and biological variation. Furthermore, the degree of both these aspects may vary according to trial type. Going forward, we should encourage all HF trials to appraise their recruitment log and suggest reasons for any reported sex disparity.


Effect of nurse colposcopists on a hospital-based service.
The number of colposcopies performed annually in the UK is increasing. Nurse colposcopists have been introduced by many units to cope with this workload. The small amount of evidence to support the introduction of nurse colposcopists suggests that nurses are viable alternative providers of colposcopy. This study compares the performance of nurse colposcopists with that of doctors.


Long-term effects of palate repair on craniofacial morphology in patients with unilateral cleft lip and palate.
To identify the long-term effects of palate repair on craniofacial growth in patients with unilateral cleft lip and palate (UCLP). Retrospective cross-sectional study. Sri Lankan Cleft Lip and Palate Project. Forty-eight adults with nonsyndromic unilateral cleft lip and palate, 29 men and 19 women, had lip repair only (LRO group). Fifty-eight adults with nonsyndromic unilateral cleft lip and palate, 35 men and 23 women, had lip and palate repairs by the age of 9 (LPR group). Clinical notes were used to record surgical treatment histories. Cephalometry was used to determine craniofacial morphology. In the lip and palate repair group, the depth of the bony pharynx (Ba-PMP), the maxillary length at the alveolar level (PMP-A), the effective length of the maxilla (Ar-IZ, Ar-ANS, Ar-A), the maxillary protrusion (S-N-ANS, SNA), the anteroposterior jaw relation (ANS-N-Pog, ANB), and the overjet were smaller than in the lip repair only group. There were no significant differences in the maxillary length at the basal level (PMP-IZ, PMP-ANS) and the anterior and posterior maxillary heights (N-ANS and R-PMP, respectively) in the two groups. Palate repair inhibits the forward displacement of the basal maxilla and anteroposterior development of the maxillary dentoalveolus in patients with unilateral cleft lip and palate. Palate repair has no detrimental effects on the downward displacement of the basal maxilla or on palatal remodeling in patients with unilateral cleft lip and palate.


Incontinence and Nocturia in Older Adults After Hip Fracture: Analysis of a Secondary Outcome for a Parallel Group, Randomized Controlled Trial.
Objective: To test the effect of a follow-up clinic on urinary incontinence (UI) and nocturia among older adults with hip fracture. Method: Fifty-three older adults (≥65 years) 3 to 12 months following hip fracture were enrolled and randomized to receive usual care plus the intervention (B4), or usual care (UC) only. The B4 group received management by health professionals, with need-based referrals. UI, nocturia, and quality of life were measured with questionnaires at baseline, 6 months, and 12 months. Results: There were 48 participants included in this analysis, and at baseline, 44% of study participants self-reported UI. At final assessment, six out of 24 B4 participants and 12 out of 24 UC participants reported UI. Four out of five study participants reported nocturia at baseline; this did not decrease during the study. Discussion: Following hip fracture, many older adults report UI and most report nocturia. Health professionals should be aware of the high occurrence of urinary symptoms among older adults post hip fracture.


An Expression Release System for Heterogeneous Proteins in E.coli Mediated by the kil Gene.
An expression release system for heterogeneous proteins in Escherichia coli mediated by the colicin release gene(kil gene) was constructed. The system is based on the ability of the Kil protein to release periplasmic proteins into the growth medium. beta-lactamase, an E.coli periplasmic protein, and prolyl endopeptidase (PEP), a periplasmic protein of Aeromonas punctata subsp. punctata were used as report proteins. Commonly, these two proteins are seldom released into the growth medium. The results indicated that the released amounts of the beta-lactamase and of the prolyl endopeptidase were nearly 5 fold and 4 fold than control, respectively.


Patient counseling practices in U.S. pharmacies: effects of having pharmacists hand the medication to the patient and state regulations on pharmacist counseling.
To determine the amount and type of oral counseling given to shoppers posing as new patients with new prescriptions and to determine how state regulations, pharmacy and pharmacist characteristics, and environmental factors affect oral counseling practices. Cross-sectional, observational, correlational study. 41 states and the District of Columbia between January 28 and March 31, 2008. 365 community pharmacy staff members had interactions with shopper-patients. Shoppers presented new prescriptions in community pharmacies and recorded observations related to oral communication with pharmacy staff. Oral provision of medication information and risk information to shoppers by pharmacy staff, as well as questions asked of shoppers by pharmacy staff. Some form of oral communication related to a medication was reported in 68% of encounters. At least one informational item for either medication was provided for approximately 42% of encounters. At least one risk information item was provided in 22% of encounters. Logistic regression findings indicated that the strongest predictor of oral counseling, either providing information or asking questions, was the pharmacist being the pharmacy staff member who handed the medication to the patient, controlling for all other variables in the models. In addition, having strict state regulations specifying that pharmacists must counsel all patients receiving new prescriptions predicted whether patients received counseling. A more private area for prescription pick up also was a significant predictor. The importance of the direct encounter between the pharmacist and patient and strict state regulations mandating that pharmacists counsel patients with new prescriptions were highlighted by these findings.


Human anti-mouse IgM and IgG responses in ovarian cancer patients after radioimmunotherapy with 90Y-muHMFG1.
Human anti-mouse antibody (HAMA)-IgM and IgG in ovarian cancer patients treated with intraperitoneal (i.p.) 90Y-muHMFG1 as consolidating therapy were analyzed for a relationship with outcome of disease. Serial serum samples from 208 ovarian cancer patients participating in a phase III trial of i.p. 90Y-muHMFG1 and 25 controls were analyzed for HAMA-IgM and HAMA-IgG. Results were correlated with time to, and location of, disease recurrence. Patients receiving i.p. 90Y-muHMFG1 developed a rapid HAMA-IgM peak (week 4 to 8), followed by a HAMA-IgG peak 2-4 weeks later. HAMA levels in the control group remained unchanged. Early maximum HAMA-IgG peaks were associated with early relapse [hazard ratio (HR), 0.975; 95% confidence interval (CI) 0.956 to 0.995; p=0.012]. Patients with a HAMA-IgG maximum before or at 8 weeks were at significantly higher risk for disease recurrence (HR, 1.6; 95% CI 1.1 to 25;p=0.021) as compared to patients with a HAMA-IgG maximum after 8 weeks. Besides time point of maximum HAMA-IgG, no evident relation could be found between HAMA-IgM or HAMA-IgG development and time to relapse or location of recurrence.


A microfluidics platform for in vitro testing.
A microfluidics system, together with a novel biosensor based on magnetic actuation of colloidal particles, enables the production of handheld diagnostic testing devices. Using this technology, a disposable diagnostic tester with short bioassay times for drugs of abuse has been developed as well as a platform to produce disposable devices for several other applications.


Selective Extraction of Flavonoids from Sophora flavescens Ait. by Mechanochemistry.
Flavonoids from Sophora flavescens were selectively extracted by mechanochemical-promoted extraction technology (MPET) after using response surface methodology to determine the optimal extraction parameters. The highest yield of 35.17 mg/g was achieved by grinding the roots with Na₂CO₃ (15%) at 440 rpm/min for 17.0 min and water was used as the sole solvent with a ratio of solvent to solid material of 25 mL/g. Flavonoids prepared by MPET demonstrated relatively higher antioxidant activities in subsequent DPPH and hydroxyl radical scavenging assays. Main constituents in the extracts, including kurarinol, kushenol I/N and kurarinone, were characterized by HPLC-MS/MS, indicating good selective extraction by MPET. Physicochemical property changes of powder during mechanochemical milling were identified by scanning electron microscopy, X-ray powder diffraction, and UV-Vis diffuse-reflectance spectroscopy. Compared with traditional extraction methods, MPET possesses notable advantages of higher selectivity, lower extraction temperature, shorter extraction time, and organic solvent free properties.


Free energy calculations: an efficient adaptive biasing potential method.
We develop an efficient sampling and free energy calculation technique within the adaptive biasing potential (ABP) framework. By mollifying the density of states we obtain an approximate free energy and an adaptive bias potential that is computed directly from the population along the coordinates of the free energy. Because of the mollifier, the bias potential is "nonlocal", and its gradient admits a simple analytic expression. A single observation of the reaction coordinate can thus be used to update the approximate free energy at every point within a neighborhood of the observation. This greatly reduces the equilibration time of the adaptive bias potential. This approximation introduces two parameters: strength of mollification and the zero of energy of the bias potential. While we observe that the approximate free energy is a very good estimate of the actual free energy for a large range of mollification strength, we demonstrate that the errors associated with the mollification may be removed via deconvolution. The zero of energy of the bias potential, which is easy to choose, influences the speed of convergence but not the limiting accuracy. This method is simple to apply to free energy or mean force computation in multiple dimensions and does not involve second derivatives of the reaction coordinates, matrix manipulations nor on-the-fly adaptation of parameters. For the alanine dipeptide test case, the new method is found to gain as much as a factor of 10 in efficiency as compared to two basic implementations of the adaptive biasing force methods, and it is shown to be as efficient as well-tempered metadynamics with the postprocess deconvolution giving a clear advantage to the mollified density of states method.


Effects of a lipid lowering fibrate and hormone replacement therapy on serum lipids and lipoproteins in overweight postmenopausal women with elevated triglycerides.
Cardiovascular disease (CVD) is the leading cause of death in women after menopause. In essence major risk factors for CVD are similar in women as for men inclusive of serum lipid perturbations. The effects of estrogens and hormone replacement therapy on lipid metabolism is widely discussed and warrant further evaluation especially when combined with other lipid lowering drugs. Postmenopausal women were studied by an open randomised study during 9 months. Subjects were recruited from outpatient clinics in a rural area of Sweden. Major inclusive criteria comprised body mass index (BMI) >28, serum triglycerides >1.5 mmol/l. Participants were at least 12 months postmenopause with a concomitant serum Follicle Stimulating Hormone (FSH) above 28 IU/l. After inclusion in the study patients were instructed to adhere to a low-fat and caloric diet for 3 months and after this period randomised into two groups of intervention; a lipidlowering fibrate (LLF) group and one hormone replacement therapy group (HRT). The LLF group was given gemfibrozil 600 mg orally twice daily and HRT group received 2 mg oestradiol in combination with 1 mg norethisterone acetate as a continuous combined therapy once daily. After 3 months, the LLF group added the HRT regimen and patients in the HRT group added gemfibrozil. Hence, all participants received the regimens combined for the last 6 months of the study. Serum s-cholesterol was markedly decreased in both groups during the first 3 months of single treatment (P<0.0001). This decrease reflected a reduction especially of calculated low density lipoprotein (LDL) s-cholesterol (P<0.001). High density lipoprotein (HDL) s-cholesterol was reduced in the HRT group (P<0.005) but increased (P<0.004) in the LLF group. Triglycerides were also decreased by both treatments but more marked in the LLF group (P<0.0001) than in the HRT group (P<0.02). After 9 months the reduction remained in both groups but no additive effects were encountered in any of the groups. The effects by gemfibrozil on s-cholesterol and triglycerides levels seem to be superior to continuous combined HRT in overweight women with elevated triglycerides. The combination of the two drugs did not seem to offer any additional benefit concerning the routine serum lipid or lipoprotein profile.


[Mobile application "Aterostop" for a comprehensive assessment of cardiovascular risk in patients in the Russian population].
The article provides an overview of an innovative software product for a comprehensive assessment of cardiovascular risk in cardiac patients in the Russian Federation. Based on the new recommendations of the Russian National Atherosclerosis Society (2020), the Aterostop application allows to assess cardiovascular risk, determine the patients achievement of target levels of low-density lipoprotein cholesterol, and also provides recommendations for correcting lipid-lowering therapy. The calculator is implemented as a web browser version, as well as a mobile application for Android and iOS platforms.


Successful management of passenger lymphocyte syndrome in an ABO-compatible, nonidentical isolated bowel transplant: a case report and review of the literature.
Passenger lymphocyte syndrome (PLS), a subtype of graft-versus-host disease, is a rare disorder encountered mainly in ABO-mismatched hematopoietic stem cell transplantation and infrequently in all types of ABO-mismatched solid organ transplantation. We here report the fifth case of PLS in small bowel transplantation (SBTx) and the first one describing the successful management of PLS in a cadaveric, isolated SBTx. A 60-year-old Caucasian female with blood group A D+ suffering from short bowel syndrome received a small bowel transplant from a 32-year-old Caucasian female with blood group O D+ (HLA mismatch 2/6). After onset of massive hemolysis on Postoperative Day 9 the positive direct and indirect antiglobulin tests showing antibodies against A1 and A2 red blood cells (RBCs) led to the diagnosis of PLS. This complication was successfully treated by transfusion of blood group O RBC transfusions, increased immunosuppression, and plasmapheresis. In the event of severe hemolysis and anemia after ABO-mismatched SBTx, PLS should be considered. In our case successful treatment consisted of transfusion of donor-specific RBCs, increased immunosuppression, and plasmapheresis.


Revisiting imidazolium based ionic liquids: Effect of the conformation bias of the [NTf2] anion studied by molecular dynamics simulations.
We study ionic liquids composed of 1-alkyl-3-methylimidazolium cations and bis(trifluoromethyl-sulfonyl)imide anions ([C n MIm][NTf2]) with varying chain-length n = 2, 4, 6, 8 by using molecular dynamics simulations. We show that a reparametrization of the dihedral potentials as well as charges of the [NTf2] anion leads to an improvement of the force field model introduced by Köddermann, Paschek, and Ludwig [ChemPhysChem 8, 2464 (2007)] (KPL-force field). A crucial advantage of the new parameter set is that the minimum energy conformations of the anion (trans and gauche), as deduced from ab initio calculations and Raman experiments, are now both well represented by our model. In addition, the results for [C n MIm][NTf2] show that this modification leads to an even better agreement between experiment and molecular dynamics simulation as demonstrated for densities, diffusion coefficients, vaporization enthalpies, reorientational correlation times, and viscosities. Even though we focused on a better representation of the anion conformation, also the alkyl chain-length dependence of the cation behaves closer to the experiment. We strongly encourage to use the new NGOLP (Neumann, Golub, Odebrecht, Ludwig, Paschek) force field for the [NTf2] anion instead of the earlier KPL parameter set for computer simulations aiming to describe the thermodynamics, dynamics, and also structure of imidazolium-based ionic liquids.


On the nucleus endymalis of the human thalamus.
In the present article the shape and extent of the nucleus endymalis in the human thalamus is described. By means of a newly developed method of selective staining of intracellular lipofuscin granules with aldehydefuchsin it is possible to examine the three-dimensional shape of the griseum in complete series of 800 micrometer thick slices. The nucleus endymalis can be divided into an invariably occurring strongly pigmented caudal pars pigmentosa with clear-cut boundaries and an oral pars commissuralis. The weakly pigmented oral part is only found in brains with developed massa intermedia and varies considerably from individual to individual. The pars pigmentosa is characterized by its periventricular position medial to the nucleus parafascicularis. Differences in nomenclature and outlines of topographically corresponding thalamic nuclei of other authors are discussed. It is assumed that the pars pigmentosa a least partly corresponds to the catecholaminergic cell group A11 in the rat brain (Dahlström and Fuxe 1964). Finally, its possible functional connections to the dorsal periventricular bundle and its significance for stimulation-produced analgesia (SPA) in man are discussed.


Cardiac magnetic resonance imaging in right ventricular outflow tract arrhythmia: a retrospective analysis from a tertiary care centre in South India.
Arrhythmia arising from right ventricular outflow tract (RVOT) is the most common cause of idiopathic ventricular arrhythmia. Previous studies involving cardiac magnetic resonance imaging (MRI) in these patients are known to show abnormalities in up to 60% of patients. This was a retrospective descriptive analysis of patients having idiopathic RVOT arrhythmia who underwent cardiac MRI between January 2010 and December 2020. Clinical and demographic details were recorded from the electronic medical records and cardiac MRI of all patients were reviewed. Among 214 patients with RVOT arrhythmia, 64 underwent cardiac MRI. A total of 41 patients, who did not have any abnormality on baseline echocardiogram were included in the study. There was male preponderance (56.1%), with median age of 43 years. About 43.9% had syncope. Twenty-four-hour Holter study revealed a premature ventricular complex (PVC) burden of 26.3 ± 11.7%. MRI showed structural abnormalities in 51.2% of patients, which commonly included RV sacculations and aneurysms. Late gadolinium enhancement (LGE) was seen in six patients, which was mostly seen in RV free wall. Right ventricular (RV) systolic dysfunction was evident in 29.3%. About 9.8% fulfilled the criteria for arrhythmogenic RV cardiomyopathy (ARVC). Out of 23 patients with baseline abnormalities on ECHO, 87% had structural abnormalities on MRI, and 43.5% fulfilled the criteria for ARVC. Additional imaging by cardiac MRI helps to identify structural abnormalities in 51.2% of patients with RVOT arrhythmias, even with normal baseline echocardiogram and electrocardiogram (ECG). It is useful tool to rule out ARVC in this subset of patients, and can help in increasing the diagnostic yield in the early stages.


Hemodynamics in arterial reconstructions of the lower limb. II. Blood pressure.
In order to demonstrate common pressure gradients and peripheral arterial pressure in ileo-femoro-popliteal arteries before and after reconstruction for atherosclerosis, intra-operative pressure measurements were performed on 204 patients. Before reconstruction, the pressure differential was 44.3 mmHg in femoro-popliteal arteries and 29.0 mmHg in the iliac arteries. This was reduced to 8.4 and 4.1 mmHg by the reconstructions. In patients with femoro-popliteal disease, the pressure gradient was higher when gangrena or rest pain were present than when claudication was the principal symptom. When the iliac arteries were mainly involved, no such difference was seen. Postoperative gradients were slightly higher in arteries subjected to primary failure than in vessels remaining patent. The blood flow increase from intra-arterial papaverine injections accentuated existing pressure gradients and frequently disclosed gradients not manifest at basal flow rates.